Abstract： Objective To investigate the unfavorable factors of intestinal mucosa repair after the intestinal epithelial injury in vivo in a mouse model of sepsis. Methods The method of cecal ligature and puncture (CLP) was used to induce sepsis and then the intestinal mucosa damage, epithelial cell apoptosis and the number of transformed goblet cells were observed, and the concentrations of serum TNF-αt, IL-1 and TGF-β1 and TFF3 ( trefoil factor 3) in small intestinal mucosa were determined. All above various laboratory examinations were made by different assays including H-E staining, western blot, ELISA and immunohistochemistry respectively. The experimental mice were divided into sepsis group and sham operation control group. The mice with sepsis were separately sacrificed 6 hours ( n = 7 ), 24 hours ( n = 7) and 48 hours ( n = 7) after CLP. Results In septic mice group, the injured intestinal mucosa was found 6 hours after CLP. The damage scores in mice 24 h and 48 h after CLP were higher than those 6 h after CLP, but there was no significant difference between those 24 h and 48 h after CLP. Moreover, a few goblet cells or other epithelial cells adjacent to the injured surface migrated onto the wound to cover the denuded area. The number of goblet cells was substantially decreased in mice of sepsis group 6 hours after CLP compared with sham operation control group. Compared with sham operation control group, levels of IL-1 and TNF-α significantly increased 3-4 times in mice of sepsis group at all intervals, and the phosphorylated caspase-3 increased 4 times. Although TFF3 assayed by using Western blot showed modest increase 6 h after CLP and it declined 24 h and 48 h later. A similar change was found in TGF-β1, it modestly increased 6h after CLP, but it didn't elevate 24 h and 48 h later. Conclusions Severe sepsis keeps on the inflammatory reaction and epithelial cell apoptosis, preventing the repair of intestinal mucosa from injury.